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Biomedical subjects

H Stein

Publications and source records attributed to H Stein.

At least 523 records · Page 29Linked to original sources

Histiocytic necrotizing lymphadenitis without granulocytic infiltration (Kikuchi's lymphadenitis). Morphological and immunohistochemical study of eight cases.

Eight examples of histiocytic necrotizing lymphadenitis without granulocytic infiltration (Kikuchi's lymphadenitis) are described. They occurred in young or middle-aged women who usually complained of latero-cervical lymphadenopathy. Serology revealed significant titres for Epstein-Barr virus and Yersinia enterocolitica serogroup 9 in one of eight and one of six tested. All patients fully recovered within 2 months. On histological examination of the lymph nodes large foci of infiltration were observed in the cortex and/or paracortex: they consisted of variable numbers of small lymphocytes, immunoblasts, macrophages and so-called plasmacytoid T-cells; granulocytes were absent. Necrotic changes varied from single pyknotic cells to extensive areas of necrosis. Immunohistochemistry showed that within the lesion the number of macrophages was inversely proportional to the number of peripheral T-lymphocytes and 'plasmacytoid T-cells'. The latter displayed a phenotype (CD4+, CD10+, CD45+) which, in the absence of macrophage-associated antigens, seemed in keeping with their supposed lymphoid nature. In seven cases peripheral T-lymphocytes predominantly expressed the cytotoxic/suppressor phenotype, while in one remaining case a mild predominance of the helper/inducer subset was observed. In the areas with less extensive tissue necrosis, numerous T-immunoblasts expressed both markers of activation and the proliferation-associated nuclear antigen Ki-67. The results of the present study expand the spectrum of our knowledge and allow speculation as to the biology of this disease.

Adolescent↗

Expression of lymphoid-associated antigens on Hodgkin's and Reed-Sternberg cells of Hodgkin's disease. An immunocytochemical study on lymph node cytospins using monoclonal antibodies.

The aim of this study was to elucidate the origin of Hodgkin's and Reed-Sternberg cells. Lymph node cytospins and frozen sections from 20 cases of Hodgkin's disease of different histological subtypes were immunostained by the immuno-alkaline phosphatase technique using a panel of monoclonal antibodies. As expected, the Hodgkin's and Reed-Sternberg cells of all cases were positive for the CD30 (Ki-1), CD15 (hapten X) and CD25 (Tac) antigens. In eight cases, a variable percentage of typical Hodgkin's and Reed-Sternberg cells showed a clear-cut cytoplasmic and/or surface positivity for the T-cell-associated antigens CD3, CD5, CD6 and CD4 (seven cases) or CD8 (one case), but consistently lacked B-cell and macrophage-associated markers. The best visualization of T-cell antigens was obtained in cytocentrifuge preparations and in areas of lymph node frozen sections that had been infiltrated by clusters of Hodgkin's and Reed-Sternberg cells. In two cases of Hodgkin's disease (nodular sclerosis, mixed cellularity) the neoplastic cells weakly expressed the B-cell antigens CD19 and CD22, but not T-cell or macrophage-associated markers. In 10 cases, Hodgkin's and Reed-Sternberg cells were negative for all the lymphoid- and macrophage-associated antigens. These results suggest a lymphoid (either T or B) rather than histiocytic origin for the Hodgkin's and Reed-Sternberg cells in a number of Hodgkin's disease cases.

Antibodies, Monoclonal↗

Genotypic analysis of large cell lymphomas which express the Ki-1 antigen.

The monoclonal antibody Ki-1 reacts with Reed-Sternberg cells in Hodgkin's disease and with the tumour cells in a minority of large cell non-Hodgkin's lymphomas. This study describes the results of immunophenotypic and DNA analysis in 30 cases of non-Hodgkin's lymphoma, all of which expressed the Ki-1 antigen. The genotypic analysis has been undertaken using both immunoglobulin and T-cell receptor gene probes. Sixteen cases were shown by this method to be of monoclonal T-cell origin, six of B-cell origin, while in eight cases there was no evidence of either T- or B-cell lineage. This confirms previous immunohistological data indicating that non-Hodgkin's lymphomas which express the Ki-1 antigen may be of either T-cell or B-cell origin.

Adolescent↗

Value of monoclonal anti-CD22 (p135) antibodies for the detection of normal and neoplastic B lymphoid cells.

Two monoclonal antibodies (To15 and 4KB128) specific for the B cell-associated CD22 antigen (135,000 mol wt) are described. On immunoenzymatic analysis of cryostat tissue sections, these antibodies strongly label both mantle zone and germinal center B lymphoid cells in secondary lymphoid follicles (and also scattered extrafollicular lymphoid cells) but are unreactive with other cell types (with the exception of weak reactivity with some epithelioid histiocytes). These reactions differ from those of monoclonal antibodies B1 and B2 (anti-CD20 and CD21) but are similar to those of the pan-B antibody B4 (anti-CD19). One of the anti-CD22 antibodies (To15) has been tested extensively by immunoenzymatic labeling on greater than 350 neoplastic lymphoid and hematological samples. The CD22 antigen was found in tissue sections in most B cell-derived neoplasms, the major exceptions being myeloma (all cases negative) and a small proportion of high-grade lymphoma (6% of cases negative). In cell smears, the antigen could be found on neoplastic cells in most B cell lymphoproliferative disorders, including common acute lymphoblastic leukemia (ALL) (90% positive) and B cell chronic lymphocytic leukemia (CLL) (89% positive). We conclude that anti-CD22 antibodies are of value for identification of human B cell lymphoproliferative disorders (especially when used in conjunction with anti-CD19 antibodies). Previous reports that the CD22 antigen is absent from many B cell neoplasms are probably due to its being expressed within the cytoplasm of immature B cells rather than on their surface.

Antibodies, Monoclonal↗

Tumor cell growth fraction in Hodgkin's disease.

The growth fraction of tumor cells was studied in 45 cases of Hodgkin's disease by means of a recently developed double immunostaining technique using monoclonal antibody Ki-1, which reacts selectively with Hodgkin and Reed-Sternberg cells in tissues affected by Hodgkin's disease, and antibody Ki-67, which recognizes a cell proliferation-associated nuclear antigen. The medians of the growth fractions of the tumor cells in all histologic subtypes of Hodgkin's disease varied between 78% and 83%. In none of the cases investigated did we find a growth fraction below 50%. Furthermore, mononucleated Hodgkin cells as well as multi-nucleated Reed-Sternberg cells showed a similar Ki-67 labeling index, indicating that both tumor cell types belong to the proliferating pool of this malignancy.

Antibodies, Monoclonal↗

[Incidence of endemic sprue in Berlin (West). A retrospective study based on biopsy findings].

The incidence of celiac disease in Berlin (West) during the years 1979-1984 has been studied retrospectively by investigating the records of the local Pathological Institutes, which examine small intestinal biopsies, for the occurrence of abnormal specimens typical of celiac disease (group 1) or consistent with the diagnosis of celiac disease (group 2). Group 1 exhibited a constant average incidence of 0.74 per 100,000 inhabitants per year, while group 2 showed a small increase between 1979 and 1984, averaging 1.03 per 100,000 inhabitants per year. Classified according to age the highest incidence was seen in the 0-5 year-olds, namely 8.04 in group 1 and 10.00 in group 2. For those children born and examined during the period of investigation the values ranged between 15.8 and 64.7 per 100,000 births. Girls, with an average frequency of 1:1919 births were more often affected than boys, who averaged 1:4219 births. These figures obtained in Berlin (West) indicate only the lower ranges of incidences and will have to be further supplemented by a prospective study.

Adolescent↗

Growth fractions and estrogen receptors in human breast cancers as determined in situ with monoclonal antibodies.

The growth fraction (GF) and estrogen receptor (ER) status of 76 cases of breast cancer were investigated on frozen sections of the same tissue block by immunostaining with monoclonal antibodies (Ki-67 and anti ER antibody). In 55 cases of this series, the ER status was also determined by standard biochemical methods. Our study revealed an inverse correlation between GF and ER status. This negative relationship was most significant when both variables were determined immunohistologically in the same tissue block and less significant when GF was analyzed by immunohistology and ER status by biochemical methods. These data suggest that the immunohistologically assessed ER values characterize the receptor status of a given carcinoma better than the biochemical values, which leads to the conclusion that the immunohistologically determined close negative relationship between GF and ER reflects the actual in vivo situation of a given breast carcinoma case. However, the immunohistologic analysis also revealed that there is a proportion of exceptional cases, ie, those with a positive ER status and a large or moderately large GF. Because only half of the ER-positive breast carcinomas respond to endocrine therapy with objective remission., it is hypothesized that it might be preferentially these mentioned exceptional cases that fail to positively respond to endocrine treatment protocols.

Antibodies, Antinuclear↗

Description of a sequential staining procedure for double immunoenzymatic staining of pairs of antigens using monoclonal antibodies.

This paper describes a sequential staining procedure for double immunoenzymatic staining of pairs of antigens in frozen tissue sections and cell smears using monoclonal antibodies. This technique involves performance of an indirect immunoperoxidase sandwich (including development of the enzyme reaction) followed by an unlabelled immuno-alkaline phosphatase sandwich (the APAAP method). The two enzyme labels are revealed using DAB/H2O2 for peroxidase and naphthol AS-MX plus fast blue or fast red for alkaline phosphatase. When compared with a hapten-sandwich/biotin-avidin system, the sequential staining procedure proved to be simpler and more sensitive and was also more suitable for double immunoenzymatic staining when monoclonal antibodies were only available in small amounts. The sequential staining procedure is particularly useful for the identification of antigens distributed in different cell populations or in different sites (e.g., nucleus and cytoplasm or cell surface) of the same cell. In contrast, this method does not appear to be very suitable for demonstrating two antigens located in the same site (e.g., surface membrane) of the same cell for which purpose double immunofluorescence remains the first choice.

Alkaline Phosphatase↗

Peptide analogues of angiotensinogen. Effect of peptide chain length on renin inhibition.

Renin inhibition was evaluated for a series of peptide analogues of angiotensinogen with different chain lengths. Systematic deletion of amino acid residues from the hexapeptide BocPheHisLeuR-ValIleHisOCH3 showed that the presence of residues at the N-terminal Phe and His positions was essential for efficient enzyme-inhibitor binding whereas the C-terminal Ile and His residues were much less important. Synthesis of a tetrapeptide analogue shortened at the C-terminus and containing modified side chains produced a potent inhibitor of renin which demonstrated hypotensive activity in a salt depleted monkey.

Amino Acid Sequence↗

Determination of the growth fraction in cell suspensions by flow cytometry using the monoclonal antibody Ki-67.

A novel procedure for determining the growth fraction of cell suspensions by flow cytometry is described. This method identifies proliferating cells by binding the monoclonal antibody Ki-67 to a nuclear antigen present in all cells that are in the G1, S, G2, and M phase of the cell cycle, but not in the G0 phase. In a kinetic study of Na cell line U937 using concanavalin A for stimulation of peripheral blood mononuclear cells, a steady increase of Ki-67 positive cells evaluated by flow cytometry was observed. Simultaneously, the [3H]thymidine uptake of the ConA blasts was measured and compared to the expression of Ki-67. A linear correlation between the percentage of Ki-67 positive cells and the log transformed counts per minute was demonstrated, and staining with Ki-67 detected cell proliferation with the same sensitivity as 3H-TdR uptake. In addition, it was possible to stain Ki-67-labelled cells with a second cell marker if a second fluorescent dye coupled to an antibody was used. This provided the opportunity to define precisely the phenotype of proliferating cells. Conversely, the number of proliferating cells expressing certain preselected surface markers could be easily determined.

Antibodies, Monoclonal↗

Improved grading of bone tumors with the monoclonal antibody Ki-67.

A total of 60 bone tumors and tumor-like lesions presenting various grades of malignancy were investigated immunohistologically with the monoclonal antibody Ki-67 directed against a cell proliferation-associated nuclear antigen. The results obtained agree well with those of flow cytometric and autoradiographic studies on similar tumor entities. The monoclonal antibody Ki-67 was found to be a handy and reliable tool for improved grading of bone tumors.

Antibodies, Monoclonal↗

Immunophenotyping of T-lymphoblastic lymphoma/leukemia: correlation with normal T-cell maturation.

Twenty-nine cases of T-lymphoblastic lymphoma/leukemia were classified with conventional morphologic methods and the aid of monoclonal antibodies. All cases were investigated with a sensitive immunohistochemical method, using a panel of 22 monoclonal antibodies. In addition, normal thymus glands in the 22nd and 36th weeks of gestation were studied. Eight different groups of T-lymphoblastic lymphomas/leukemias could be distinguished, each of which showed a characteristic marker constellation. The results indicate that a complete detection of all thymic and prethymic lymphomas and leukemias is possible. By comparison with the phenotypic pattern of normal peripheral T-lymphocytes and their thymic precursors, the groups could be arranged in a sequence that resembles normal T-cell maturation, monoclonal antibodies.

Adolescent↗

T-cell growth factor receptor (Tac-antigen) expression in cutaneous lymphoid infiltrates.

A total of ninety-four biopsies from normal skin, benign dermatoses, and lesions of human T cell lymphotropic virus type I (HTLV-I)-positive and -negative cutaneous T cell disorders have been examined immunohistologically for reactivity with anti-Tac (monoclonal anti-T cell growth factor receptor). Tac-positive T cells were plentiful in approximately half the specimens, and they were equally frequent in benign and malignant disorders and in HTLV-I-positive and -negative cutaneous T cell disorders. Furthermore, in diseased skin, reactivity with anti-Tac was not confined to T lymphocytes, since it was also a property of dermal macrophages and Langerhans cells, as shown by examination of serial and/or double-stained sections. Comparison with other markers linked to T cell activation and proliferation (i.e., HLA-DR, OKT10 antigen, transferrin receptor, and the Ki-67 nuclear antigen) showed that Tac-antigen expression did not correlate clearly with any of these markers. These data indicate that anti-Tac forms a useful supplement to other monoclonal antibodies for the identification of activated cell subsets in cutaneous lymphoid infiltrates, but they also show that the use of this reagent on cutaneous biopsy specimens is of only limited diagnostic value.

Antibodies, Monoclonal↗

Reed-Sternberg and Hodgkin cells in lymphocyte-predominant Hodgkin's disease of nodular subtype contain J chain.

To throw light on the question of whether B-cell-derived forms of Hodgkin's disease exist, more than 100 cases of Hodgkin's disease (including all four major histologic categories) were investigated for the presence of J chain and were also immunostained for epithelial membrane antigen and the granulocyte-associated antigen X hapten. Reed-Sternberg and Hodgkin cells (RS & H) expressed J chain in 22 cases, 8 of which also expressed epithelial membrane antigen (EMA). X hapten was found in 62 cases, but all of these were J chain negative. J chain-positive RS & H cells were restricted to cases of lymphocyte-predominant disease, while X hapten-positive tumor cells were found frequently in nodular sclerosis, mixed cellularity, and lymphocyte-depletion Hodgkin's disease, but only occasionally in cases of lymphocyte-predominant disease. These findings indicate that nodular lymphocyte-predominant Hodgkin's disease differs from the other subtypes of Hodgkin's disease and that the neoplastic cells are of B-lymphoid origin.

Fluorescent Antibody Technique↗

Expression of a cell-cycle-associated nuclear antigen (Ki-67) in cutaneous lymphoid infiltrates.

Cryostat sections of skin biopsies from 83 patients with benign or malignant cutaneous lymphoid infiltrates were examined immunohistologically for reactivity with Ki-67 (a monoclonal antibody recognizing a nuclear antigen expressed by cycling cells) using the APAAP immunoalkaline phosphatase labeling method and a double immunoperoxidase/alkaline phosphatase staining technique. Ki-67-positive neoplastic lymphocytes were plentiful in all large-cell lymphoma cases and in one-third of the small-cell lymphomas. Some benign disorders (patch test biopsies, cutaneous lymphocytoma, lichen planus) also contained many Ki-67-positive lymphocytes. These data indicate the value of using Ki-67 to assess the proliferative capacities of the lymphoid cells in cutaneous infiltrates. Use of this technique in the future may have important prognostic and therapeutic implications in the management of cutaneous lymphoid malignancies.

Antibodies, Monoclonal↗